Characterize the vasculatures distribution of murine tumors between center and peripheral regions based on Doppler ultrasound and immunofluorescent analysis

The tumor microenvironment changes are an important prognostic indicator for assessment of therapeutic efficacy, especially tumor vasculatures, because the delivery efficiency of drugs and oxygen is dependent on the perfusion and distribution of the tumor vasculature. Since, the heterogeneity of tumors is the main obstacle to treatment, observing the information about tumor behaviors within the central and peripheral regions of a tumor could be helpful for improving tumor therapies. Murine tumors were monitored for 11 days. The tumor perfusion was estimated by means of power Doppler images at a central frequency of 25 MHz. Tumors were removed for immunohistochemical analysis of their vascular density using CD31 staining at each analysis time point. The spatial characteristics of the tumor vasculature were quantified by calculating the γ value derived from fitting with a power-law transformation for different fractions of the peripheral area. During tumor progression, the γ value significantly decreased in the power Doppler images but not in the immunohistochemical analysis. These results suggest that the perfusion spread more in peripheral region of the tumor than in the central region while the vascular density still appear evenly distributed. Observing the information of tumor behaviors within center and peripheral tumor regions by spatial analysis will be useful in adjusting dose of treatment for optimal strategies.